Boron–Oxygen Chelation‐Enabled Aza‐BODIPY <i>J</i> ‐Aggregates: NIR‐II Imaging and Photothermal Therapy for Single‐Dose Tumor Ablation

Integrating high-performance near-infrared-II (NIR-II, 900-1880 nm) fluorescence imaging with efficient photothermal therapy (PTT) in a single nanoplatform remains a formidable challenge in cancer theranostics. Herein, a supramolecular engineering strategy leveraging boron-oxygen (B-O) chelation is presented to construct conformationally locked aza-BODIPY derivatives (BTA-BDP) that self-assemble into ultrastable J-aggregates. This design achieves dual breakthroughs: 1) a fluorescence quantum yield (Φ) of 4.37% in the NIR-II window (λ_em = 1014 nm), surpassing the typical Φ < 1% barrier for NIR-II emitters; and 2) a record photothermal conversion efficiency (PCE) of 69.6%, exceeding most organic photothermal agents (PCE < 50%). Molecular dynamics simulations and pharmacokinetic studies reveal that the combination of strong π-π stacking interactions and long alkyl chains prolongs tumor retention (>344 h), enabling single-dose administration. Under low-power 808 nm irradiation (0.4 W cm^- ²), BTA-BDP nanoparticles (NPs) induce rapid hyperthermia (ΔT = 25.9 °C) and complete tumor ablation in murine models, validated by histopathology and multimodal imaging (NIR-II/photoacoustic). This work resolves the fluorescence-photothermal trade-off and establishes a supramolecular blueprint for precision cancer nanomedicine, thereby bridging the gap between molecular engineering and clinical translation.